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These two mRNA isoforms, remarkably different in the sequence and length of their <jats:italic>3\u2032UTRs<\/jats:italic>, are potentially involved in distinct post-transcriptional regulatory circuits. Herein, we identify PARP1 among the mRNA Binding Proteins that specifically target the <jats:italic>X1 3\u2032UTR<\/jats:italic> in melanoma cells. Mechanistically, PARP1 Zinc Finger domain down-regulates <jats:italic>BRAF<\/jats:italic> expression at the translational level. As a consequence, it exerts a negative impact on MAPK pathway, and sensitizes melanoma cells to BRAF and MEK inhibitors, both in vitro and in vivo. In summary, our study unveils PARP1 as a negative regulator of the highly oncogenic MAPK pathway in melanoma, through the modulation of <jats:italic>BRAF<\/jats:italic>-<jats:italic>X1<\/jats:italic> expression.<\/jats:p>","DOI":"10.1186\/s13045-023-01428-2","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T16:09:19Z","timestamp":1680538159000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["PARP1 negatively regulates MAPK signaling by impairing BRAF-X1 translation"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8334-8795","authenticated-orcid":false,"given":"Andrea","family":"Marranci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Prantera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Masotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"De Paolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Baldanzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio S.","family":"Podda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Mero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Vitiello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Franchin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariavittoria","family":"Laezza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Comelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Arrigoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Cervelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Del Pozzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6557-955X","authenticated-orcid":false,"given":"Laura","family":"Poliseno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,3]]},"reference":[{"key":"1428_CR1","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1007\/s10555-020-09884-9","volume":"39","author":"AE Erson-Bensan","year":"2020","unstructured":"Erson-Bensan AE. RNA-biology ruling cancer progression? Focus on 3\u2032UTRs and splicing. Cancer Metastasis Rev. 2020;39:887\u2013901.","journal-title":"Cancer Metastasis Rev"},{"key":"1428_CR2","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s12943-017-0645-4","volume":"16","author":"A Marranci","year":"2017","unstructured":"Marranci A, Jiang Z, Vitiello M, Guzzolino E, Comelli L, Sarti S, et al. The landscape of BRAF transcript and protein variants in human cancer. Mol Cancer. 2017;16:66.","journal-title":"Mol Cancer"},{"key":"1428_CR3","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/s41388-018-0496-5","volume":"38","author":"S Lubrano","year":"2019","unstructured":"Lubrano S, Comelli L, Piccirilli C, Marranci A, Dapporto F, Tantillo E, et al. Development of a yeast-based system to identify new hBRAFV600E functional interactors. 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